| Structural highlights
Function
ZNT7_HUMAN Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway (PubMed:15525635, PubMed:15994300). By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases (PubMed:15525635, PubMed:15994300).[1] [2]
Publication Abstract from PubMed
Zinc ions (Zn(2+)) are vital to most cells, with the intracellular concentrations of Zn(2+) being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 A-resolution cryo-EM structures of a Golgi-localized human Zn(2+)/H(+) antiporter ZnT7 (hZnT7) in Zn(2+)-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn(2+)-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn(2+) entry in the inward-facing conformation and widens the luminal cavity for Zn(2+) release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn(2+) ions, seemingly facilitating Zn(2+) recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn(2+) uptake into the Golgi to be proposed.
Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn(2+) uptake into the Golgi apparatus.,Bui HB, Watanabe S, Nomura N, Liu K, Uemura T, Inoue M, Tsutsumi A, Fujita H, Kinoshita K, Kato Y, Iwata S, Kikkawa M, Inaba K Nat Commun. 2023 Aug 8;14(1):4770. doi: 10.1038/s41467-023-40521-5. PMID:37553324[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Suzuki T, Ishihara K, Migaki H, Matsuura W, Kohda A, Okumura K, Nagao M, Yamaguchi-Iwai Y, Kambe T. Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane. J Biol Chem. 2005 Jan 7;280(1):637-43. PMID:15525635 doi:10.1074/jbc.M411247200
- ↑ Suzuki T, Ishihara K, Migaki H, Ishihara K, Nagao M, Yamaguchi-Iwai Y, Kambe T. Two different zinc transport complexes of cation diffusion facilitator proteins localized in the secretory pathway operate to activate alkaline phosphatases in vertebrate cells. J Biol Chem. 2005 Sep 2;280(35):30956-62. PMID:15994300 doi:10.1074/jbc.M506902200
- ↑ Bui HB, Watanabe S, Nomura N, Liu K, Uemura T, Inoue M, Tsutsumi A, Fujita H, Kinoshita K, Kato Y, Iwata S, Kikkawa M, Inaba K. Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn(2+) uptake into the Golgi apparatus. Nat Commun. 2023 Aug 8;14(1):4770. PMID:37553324 doi:10.1038/s41467-023-40521-5
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